Molecular mechanisms behind progressing chronic inflammatory dilated cardiomyopathy

Background: Inflammatory dilated cardiomyopathy (iDCM) is a common debilitating disease with poor prognosis that often leads to heart failure and may require heart transplantation. The aim of this study was to evaluate sera and biopsy samples from chronic iDCM patients, and to investigate molecular mechanism associated with left ventricular remodeling and disease progression in order to improve therapeutic intervention. Methods: Patients were divided into inflammatory and non-inflammatory DCM groups according to the immunohistochemical expression of inflammatory infiltrates markers: T-lymphocytes (CD3), active-memory T lymphocyte (CD45Ro) and macrophages (CD68). The inflammation, apoptosis, necrosis and fibrosis were investigated by ELISA, chemiluminescent, immunohistochemical and histological assays. Results: The pro-inflammatory cytokine IL-6 was significantly elevated in iDCM sera (3.3 vs. 10.98 μg/ml; P < 0.05). Sera levels of caspase-9, −8 and −3 had increased 6.24-, 3.1- and 3.62-fold, (P  < 0.05) and only slightly (1.3-, 1.22- and 1.03-fold) in biopsies. Significant release of Hsp60 in sera (0.0419 vs. 0.36 ng/mg protein; P < 0.05) suggested a mechanistic involvement of mitochondria in cardiomyocyte apoptosis. The significant MMP9/TIMP1 upregulation in biopsies (0.1931 - 0.476, P < 0.05) and correlation with apoptosis markers show its involvement in initiation of cell death and ECM degradation. A slight activation of the extrinsic apoptotic pathway and the release of hsTnT might support the progression of chronic iDCM. Conclusions: Data of this study show that significant increase of IL-6, MMP9/TIMP1 and caspases-9, −8, −3 in sera corresponds to molecular mechanisms dominating in chronic iDCM myocardium. The initial apoptotic pathway was more activated by the intramyocardial inflammation and might be associated with extrinsic apoptotic pathway through the pro-apoptotic Bax. The activated intrinsic form of myocardial apoptosis, absence of necrosis and decreased fibrosis are most typical characteristics of chronic iDCM. Clinical use of anti-inflammatory drugs together with specific anti-apoptotic treatment might improve the efficiency of therapies against chronic iDCM before heart failure occurs

Prostate cancer solitary metastasis to anal canal: case report and review of literature

Abstract Background Here we present the first cases of prostate cancer solitary metastasis to anal canal. Case presentation A 67-year-old male patient underwent radical prostatectomy with ilio-obturator lymphonodectomy in 2016 due to poorly differentiated ductal adenocarcinoma (Gleason 4 + 5(40%) = 9) pT3bN0. Two months later increasing PSA rate was noted and the patient started adjuvant intermittent androgen deprivation therapy combined with radiotherapy. Year after patient was admitted to the hospital complaining of dyschezia, pain in anal canal, and bloody stool. Digital rectal examination revealed an anal fissure with ulceration. A biopsy from ulcerated area showed poorly differentiated ductal adenocarcinoma of the prostate. Because there was no evidence of distant metastases on abdominal computed tomography (CT) scan and pelvic magnetic nuclear resonance imaging (MRI) and the only metastasis was in anal canal patient underwent laparoscopic abdominoperineal resection (APR). Postoperative course was uneventful and patient was discharged at postoperative day 7. Conclusions Our presented case is the first to describe prostate cancer solitary metastasis to anal canal and we always have to be aware of possible rare disease while assessing the patient with rectal bleeding. Biopsy most of the time is the only and the most reliable test to differentiate between the diseases